The bryostatins are a family of macrocyclic lactones which have been isolated from specimens of marine bryozoans. The sea-mat Bugula neritina has been the source of many of the bryostatins. Others have been isolated from the marine animal Amathia convoluta, also a member of the phylum Bryozoa.
All of the bryostatins are derived from the bryopyran ring system (Petitt et al, Journal of Natural Products, Vol. 46, pp. 528-531, 1983) and all are reported to have antineoplastic activity aganist a single murine leukemia cell line, the P388 lymphocytic leukemia line. The bryostatins substantially inhibit P388 cell growth in vitro, and also are able to increase the life span of mice injected with P388 lymophocytic leukemia cells. Bryostatins 1-8 are described in Pettit U.S. Pat. No. 4,560,774 and U.S. Pat. No. 4,611,066.
There are many health conditions which result in a deficiency of hematopoietic cells. For example, a problem often arises in the treatment of cancers with antineoplastic agents; these agents can have an inhibitory effect on normal bone marrow progenitor cells (stem cells). In addition, there are many diseases in which neutropenias result, such as acquired immune deficiency syndrome (AIDS).
There are also many conditions in which erythroid cells are insufficient to support normal activity, such as congential anemias, and Fanconi's anemia. Diseases such as rheumatoid arthritis and lupus erythematosus, often result in depletion of certain populations of blood cells. Therefore there is a continuing need in the art for agents which are safe to administer and which stimulate the development of various types of hematopoietic cells.